Tremorolytic effects of adenosine A2A antagonists:: implications for parkinsonism

Drug-induced tremulous jaw movements in rats have been used as a model of parkinsonian tremor. Because adenosine A(2A) antagonists have antiparkinsonian effects, the present experiments were conducted to study the ability of adenosine A(2A) antagonism to reverse the tremulous jaw movements produced by the antipsychotic drugs pimozide, haloperidol and reserpine. In one group of studies, rats received daily injections of the dopamine antagonist pimozide, and on day 8 they received injections of pimozide plus various doses of the A(2A) antagonists KW 6002 or MSX-3. KW 6002 and MSX-3 suppressed pimozide-induced tremulous jaw movements, reduced catalepsy, and increased locomotion. MSX-3 also suppressed the jaw movements induced by haloperidol and reserpine. In addition, local injections of MSX-3 into the ventrolateral neostriatum suppressed pimozide-induced tremulous jaw movements. Thus, adenosine A(2A) antagonism can reverse the tremulous movements induced by antipsychotic drugs, which is consistent with the hypothesis that antagonism of adenosine A(2A) receptors can result in antiparkinsonian effects. Adenosine A(2A) antagonists may be useful for their tremorolytic effects, and may help in treating both idiopathic and antipsychotic-induced parkinsonian symptoms.